Mutational analysis and genotype/phenotype correlation in Turkish Charcot-Marie-Tooth Type I and HNPP patients

The major Charcot-Marie-Tooth Type 1 (CMT1) locus, CMT1A, and Hereditary ne uropathy with liability to pressure palsies (HNPP) cosegregate with a 1.5-M b duplication and a 1.5-Mb deletion, respectively, in band 17p11.2. Point m utations in peripheral myelin gene 22 (PMP22), myelin protein zero (MPZ), a nd connexin 32 (Cx32) have been reported in CMT1, and in PMP22 in HNPP pati ents without deletion. We have screened 54 CMT1 patients, of variable clini cal severity, and 25 HNPP patients from Turkey, with no duplication or dele tion, for mutations in the PMP22 and Cx32 genes. A novel frameshift mutatio n affecting the second extracellular domain of PMP22 was found in an HNPP p atient, while a point mutation in the second transmembrane domain of the pr otein was detected in a CMT1 patient. Two point mutations affecting differe nt domains of Cx32 were identified in two CMTX patients. Another patient wa s found to carry a polymorphism in a non-conserved codon of the Cx32 gene. The clinical phenotypes of the patients correlate well with the effect of t he mutation on the protein.